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The article presents the author's insights on the action taken by the publication "PNAS" after it clearly violated the U.S. National Institute of Health (NIH) embargo policy in relation to the Study of Addiction, Genetics and Environment (SAGE). It notes that "PNAS" has published online an article about PKNOX2 gene, but violated the policy after one of the study's authors has signed a Data Use Certification with NIH. It also examines the implications of the case to the scientific community.

The article discusses the complement of Leslie Vosshall, a neurogeneticist at the Rockefeller University in New York, and Hiroaki Matsumi and His Group at Duke University Medical Center, in Durnham, North Carolina, for the experimentation on John Amoore's research on the perception of androstenone, an odorous steroid in the urine and sweat of men in the U.S. Matsunumi arranges the coding region of the OR7D4 gene of 391, an odour receptors in tissue-culture cells, to Vosshal's volunteers. It is then, Vosshal recognizes that there is clear and strong correlation between having the functional receptor in the genome and being very sensitive to androstenone.

Studies of political attitudes and ideologies have sought to explain their origin. They have been assumed to be a result of political values ingrained during the process of socialization until early adulthood, as well as personal political experience, party affiliation, social strata, etc. As a consequence of these environment-dominated explanations, most biology-based accounts of political preference have never been considered. However, in the light of evidence accumulated in recent years, the view that political attitudes are detached from any physical properties became unsustainable. In this paper, we investigate the origins of social justice attitudes, with special focus on economic egalitarianism and its potential genetic basis. We use Minnesota Twin Study data from 2008, collected from samples of monozygotic and dizygotic twin pairs ( n = 573) in order to estimate the additive genetic, shared environmental, and unique environmental components of social justice attitudes. Our results show that the large portion of the variance in a four-item economic egalitarianism scale can be attributed to genetic factor. At the same time, shared environment, as a socializing factor, has no significant effect. The effect of environment seems to be fully reserved for unique personal experience. Our findings further problematize a long-standing view that social justice attitudes are dominantly determined by socialization. [ABSTRACT FROM AUTHOR]

The article focuses on the recent advances in biotechnology. It cites that the advances in the biotechnology have changed the key nature of biological researches. It relates that scientists in the past used paper notebooks or simple spreadsheets to document their experiments, but at present, scientists use various new tools such as gene chips or measuring gene expression or sequence variation that brought changes and has altered their works and reveals potential associations and interactions with a variety of genes and other biological entities. It also mentions that the advances in biotechnology brought a massive increase in the scientific knowledge of scientists. The establishment of the Text Retrieval Conference in the U.S. is also discussed.

Fructosamine is a measure of short-term glycemic control, which has been suggested as a useful complement to glycated hemoglobin (HbA1c) for the diagnosis and monitoring of diabetes. To date, a single genome-wide association study (GWAS) including 8,951 U.S. White and 2,712 U.S. Black individuals without a diabetes diagnosis has been published. Results in Whites and Blacks yielded different association loci, near RCN3 and CNTN5, respectively. In this study, we performed a GWAS on 20,731 European-ancestry blood donors and meta-analyzed our results with previous data from U.S. White participants from the Atherosclerosis Risk in Communities (ARIC) study (Nmeta = 29,685). We identified a novel association near GCK (rs3757840, βmeta = 0.0062; minor allele frequency [MAF] = 0.49; Pmeta = 3.66 × 10-8) and confirmed the association near RCN3 (rs113886122, βmeta = 0.0134; MAF = 0.17; Pmeta = 5.71 × 10-18). Colocalization analysis with whole-blood expression quantitative trait loci data suggested FCGRT as the effector transcript at the RCN3 locus. We further showed that fructosamine has low heritability (h2 = 7.7%), has no significant genetic correlation with HbA1c and other glycemic traits in individuals without a diabetes diagnosis (P > 0.05), but has evidence of shared genetic etiology with some anthropometric traits (Bonferroni-corrected P < 0.0012). Our results broaden knowledge of the genetic architecture of fructosamine and prioritize FCGRT for downstream functional studies at the established RCN3 locus. [ABSTRACT FROM AUTHOR]

Political interest is one of the strongest predictors of individual political engagement, but little is known about the origins of this political orientation. The goal of this paper is to clarify the role that biological and psychological factors play in the formation of political interest. A series of recent studies in genetics have illustrated that political interest is heritable, and a series of recent studies in political science and psychology have demonstrated that personality traits, many of which are heritable, are related to political interest. In this paper, we make a number of contributions to the literature: (1) we replicate previous analyses showing that political interest and personality traits are heritable, (2) we demonstrate that personality traits are related to interest, and (3) we estimate the extent to which genetic factors account for the correlation between personality traits and political interest. Using two datasets on twins, we find evidence that genetic factors account for a large amount of the correlation between political interest and personality traits. This study provides a more nuanced picture of the biological and psychological bases of political orientations. [ABSTRACT FROM AUTHOR]

Background Carbapenem-resistant Enterobacterales (CRE) are an urgent public health threat in the United States. Objective Describe the clinical and molecular epidemiology of CRE in a multicenter pediatric cohort. Methods CRACKLE-1 and CRACKLE-2 are prospective cohort studies with consecutive enrollment of hospitalized patients with CRE infection or colonization between 24 December 2011 and 31 August 2017. Patients younger than age 18 years and enrolled in the CRACKLE studies were included in this analysis. Clinical data were obtained from the electronic health record. Carbapenemase genes were detected using polymerase chain reaction and whole-genome sequencing. Results Fifty-one children were identified at 18 healthcare system study sites representing all U.S. census regions. The median age was 8 months, with 67% younger than age 2 years. Median number of days from admission to culture collection was 11. Seventy-three percent of patients had required intensive care and 41% had a history of mechanical ventilation. More than half of children had no documented comorbidities (Q1, Q3 0, 2). Sixty-seven percent previously received antibiotics during their hospitalization. The most common species isolated were Enterobacter species (41%), Klebsiella pneumoniae (27%), and Escherichia coli (20%). Carbapenemase genes were detected in 29% of isolates tested, which was lower than previously described in adults from this cohort (61%). Thirty-four patients were empirically treated on the date of culture collection, but only 6 received an antibiotic to which the CRE isolate was confirmed susceptible in vitro. Thirty-day mortality was 13.7%. Conclusions CRE infection or colonization in U.S. children was geographically widespread, predominantly affected children younger than age 2 years, associated with significant mortality, and less commonly caused by carbapenemase-producing strains than in adults. [ABSTRACT FROM AUTHOR]

In June 2013, the US Supreme Court ruled that naturally occurring genes were unpatentable in the case Association for Molecular Pathology v. Myriad Genetics. Up until this decision, Myriad Genetics was the only company in the USA that could legally conduct diagnostic testing for BRCA1 and 2, genes that are linked to familial breast and ovarian cancer. The court case and rulings garnered discussion in public about patenting biological materials. This paper will describe the progression of the Myriad Genetics case, similar US rulings and biological intellectual property policies. In addition, it will discuss the impact of the case on biological patents - specifically those for human embryonic stem cells.

Several gene databases, including heavily used ones such as the National Center for Biotechnology Information (NCBI) database, erroneously assign, on occasion, literature references to genes or proteins. These mistakes are mostly due to an overlap in gene aliases, whereby two distinct genes share a pseudonym. This is particularly confusing when the gene products have also biological properties in common, are part of signaling pathways that cross-talk to one another, or are regulated by the same effectors. We present examples spanning several research fields including apoptosis, ubiquitin-dependent degradation, signaling by Notch, Wnt, and small G proteins, transporters of glutathione conjugates of electrophiles, and mitochondrial and ribosomal RNA genes. To solve the problem, we argue in favor of including Entrez gene numbers in papers submitted for publication as unique gene identifiers to allow precise identification of genes and species studied., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The paper focuses on the fundamental debate that is going on in Europe and the United States about whether genes and genetic diagnostic methods are to be regarded as inventions or subject matter eligible for patent protection, or whether they are discoveries or principles of nature and thus excluded from patentability. The study further explores some possible scenarios of American influences on European patent applications with respect to genetic diagnostic methods. Our analysis points out that patent eligibility for genes and genetic diagnostic methods, as discussed in the United States in the Association of Molecular Pathology versus US Patent and Trademark Office decision, is based on a different reasoning compared with the European Patent Convention.

Objectives: Animal models are a key resource for the investigation of human diseases. In contrast to functional annotation, phenotype annotation is less standard, and comparing phenotypes across species remains challenging. The objective of this paper is to propose a framework for comparing phenotype annotations of orthologous genes based on the Medical Subject Headings (MeSH) indexing of biomedical articles in which these genes are discussed., Methods: 17,769 pairs of orthologous genes (mouse and human) are downloaded from the Mouse Genome Informatics (MGI) system and linked to biomedical articles through Entrez Gene. MeSH index terms corresponding to diseases are extracted from Medline., Results: 11,111 pairs of genes exhibited at least one phenotype annotation for each gene in the pair. Among these, 81% have at least one phenotype annotation in common, 80% have at least one annotation specific to the human gene and 84% have at least one annotation specific to the mouse gene. Four disease categories represent 54% of all phenotype annotations., Conclusions: This framework supports the curation of phenotype annotation and the generation of research hypotheses based on comparative studies.

Continuing the discussion begun in the March 2006 issue of the Kennedy Institute of Ethics Journal, this paper further documents the failure of the United States to adequately consider possible modifications in the traditional robust system of intellectual property rights as applied to biotechnology. It discusses concrete suggestions for alternative disclosure requirements, for exemptions for research tools, and for improved access to clinical advances. In each of these cases, the modifications might be more responsive to the full set of relevant values.

University technology transfer offices license inventions created at universities to companies looking for tools, additions to their product pipelines, improvements or start-up opportunities. This paper will cover the motivations for conducting university technology transfer, an overview of Stanford's Office of Technology Licensing and its patenting and licensing practices, models of royalty sharing at university technology transfer offices, and patenting and licensing genetic information inventions at Stanford University. The terms 'invention' and 'technology' are used interchangeably throughout the paper., (Copyright 2005 S. Karger AG, Basel)

This paper analyses the ways in which genomic knowledge is portrayed as useful knowledge in gene patenting in order to fulfil the 'utility'/'industrial applicability' requirement for patentability. It gives examples of utility claims in gene patents and asks whether genomics (as opposed to genetics) changes our ideas about what is useful and what can be patented. It puts forward a provisional classification of different types of utility and argues that merely identifying the physiological function of a gene diverges radically from our commonsense understanding of what it is for an invention to be useful. Furthermore, social, political and ethical issues inevitably arise when discussing the utility requirement, because an invention cannot be useful in isolation from a social context.

We present a method for creating a network of gene co-occurrences from the literature and partitioning it into communities of related genes. The way in which our method identifies communities makes it likely that the component genes of each community will be related by their function. The method processes a large database of article abstracts, synthesizing information from many sources to shed light on groups of genes that have been shown to interact. It is a tool to be used by researchers in the biomedical sciences to swiftly search for known interactions and to provide insight into unexplored connections. The partitioning procedure is designed to be particularly applicable to large networks in which individual nodes may play a role in more than one community. In this paper, we explain the details of the method, in particular the partitioning process. We also apply the method to produce communities of genes related to colon cancer and show that the results are useful.

Background: Physiologically-based pharmacokinetic (PBPK) modeling in predicting metabolic drug-drug interactions (mDDIs) is routinely used in drug development. Currently, the US FDA endorses the use of PBPK to potentially support dosing recommendations for investigational drugs as enzyme substrates of mDDIs, and to inform a lack of mDDIs for investigational drugs as enzyme modulators.Methods: We systematically evaluated the performance of PBPK modeling in predicting mDDIs published in the literature. Models developed to assess both investigational drugs as enzyme substrates (Groups 1 and 2, as being inhibited and induced, respectively) or enzyme modulators (Groups 3 and 4, as inhibitors and inducers, respectively) were evaluated. Predicted ratios of the area under the curve (AUCRs) and/or maximum plasma concentration (CmaxRs) with and without comedication were compared with the observed ratios.Results: For Groups 1, 2, 3, and 4, 62, 50, 44, and 43% of model-predicted AUCRs, respectively, were within a predefined threshold of 1.25-fold of observed values (0.8-1.25x). When the threshold was widened to twofold, the values increased to 100, 80, 81, and 86% (0.5-2.0x). For Groups 3 and 4, prediction for mDDI liability (the existence or lack of mDDIs) using PBPK appears to be satisfactory.Conclusion: Our analysis supports the FDA's current recommendations on the use of PBPK to predict mDDIs. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) is a major cause of chronic liver disease worldwide. Besides genotype, quantitative analysis of HBV infection is extensively used for monitoring disease progression and treatment. Affordable viral load monitoring is desirable in resource-limited settings and it has been already shown to be useful in developing countries for other viruses such as Hepatitis C virus (HCV) and HIV. In this paper, we describe the validation of a real-time PCR assay for HBV DNA quantification with TaqMan chemistry and MGB probes. Primers and probes were designed using an alignment of sequences from all HBV genotypes in order to equally amplify all of them. The assay is internally controlled and was standardized with an international HBV panel. Its efficacy was evaluated comparing the results with two other methods: Versant HBV DNA Assay 3.0 (bDNA, Siemens, NY, USA) and another real-time PCR from a reference laboratory. Intra-assay and inter-assay reproducibilities were determined and the mean of CV values obtained were 0.12 and 0.09, respectively. The assay was validated with a broad dynamic range and is efficient for amplifying all HBV genotypes, providing a good option to quantify HBV DNA as a routine procedure, with a cheap and reliable protocol. [ABSTRACT FROM AUTHOR]

Fusiform rust disease remains the most destructive disease in pine plantations in the southern United States. Our ongoing research is designed to identify, map, and clone the interacting genes of the host and pathogen. Several resistance (R) genes have been identified and genetically mapped using informative pine families and single-spore isolate inoculations. In addition, we are mapping the first of many expected corresponding avirulence (Avr) genes in the fungal pathogen. The Avr genes condition avirulence/virulence and avirulence is required for an incompatible reaction (i.e., no-gall development) to take place within an inoculated tree that carries resistance at the corresponding R gene. We provide an overview of our methodology for identifying and mapping R and Avr genes, an update of our current progress, and a brief discussion of two approaches for predicting R gene genotypes of uncharacterized parental trees and for estimating the efficacy of specific pine genotypes at various planting locations. This paper emphasizes the critical importance of controlled genetic materials of both the host and pathogen for elucidating the genetic nature of resistance and virulence in coevolved forest pathosystems. [ABSTRACT FROM AUTHOR]

Currently in the United States there is little direction for what constitutes sufficient guidelines for DNA mixture interpretation. While a standardized approach is not possible or desirable, more definition is necessary to ensure reliable interpretation of results is carried out. In addition, qualified DNA examiners should be able to review reports and understand the assumptions made by the analyst who performed the interpretation. Interpretation of DNA mixture profiles requires consideration of a number of aspects of a mixed profile, many of which need to be established by on-site, internal validation studies conducted by a laboratory’s technical staff, prior to performing casework analysis. The relevant features include: criteria for identification of mixed specimens, establishing detection and interpretation threshold values, defining allele peaks, defining nonallele peaks, identifying artifacts, consideration of tri-allelic patterns, estimating the minimum number of contributors, resolving components of a mixture, determining when a portion of the mixed profile can be treated as a single source profile, consideration of potential additive effects of allele sharing, impact of stutter peaks on interpretation in the presence of a minor contributor, comparison with reference specimens, and some issues related to the application of mixture calculation statistics. Equally important is using sensible judgment based on sound and documented principles of DNA analyses. Assumptions should be documented so that reliable descriptive information is conveyed adequately concerning that mixture and what were the bases for the interpretations that were carried out. Examples are provided to guide the community. Interpretation guidelines also should incorporate strategies to minimize potential bias that could occur by making inferences based on a reference sample. The intent of this paper is to promote more thought, provide assistance on many aspects for consideration, and to support that more formalized mixture interpretation guidelines are developed. [ABSTRACT FROM AUTHOR]

Copyright of Estudios Socio-Jurídicos is the property of Colegio Mayor de Nuestra Senora del Rosario and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Hispanic populations are a valuable resource that can and should facilitate the identification of complex trait genes by means of admixture mapping (AM). In this paper we focus on a particular Hispanic population living in the San Luis Valley (SLV) in Southern Colorado.We used a set of 22 Ancestry Informative Markers (AIMs) to describe the admixture process and dynamics in this population. AIMs are defined as genetic markers that exhibit allele frequency differences between parental populations ≥30%, and are more informative for studying admixed populations than random markers. The ancestral proportions of the SLV Hispanic population are estimated as 62.7 ± 2.1% European, 34.1 ± 1.9% Native American and 3.2 ± 1.5% West African. We also estimated the ancestral proportions of individuals using these AIMs. Population structure was demonstrated by the excess association of unlinked markers, the correlation between estimates of admixture based on unlinked marker sets, and by a highly significant correlation between individual Native American ancestry and skin pigmentation (R2= 0.082, p < 0.001). We discuss the implications of these findings in disease gene mapping efforts. [ABSTRACT FROM AUTHOR]

Controversies concerning the religious implications of science have grown increasingly strained in recent years. Creation scientists have deployed new strategies to eliminate the teaching of evolution in public schools; right-to-life groups have obstructed fetal tissue research; and clerical groups have criticized genomics and genetic testing. Meanwhile, the Templeton Foundation has begun promoting the idea that there is no conflict between science and religion. In this paper; I explore emerging efforts to reconcile religion and science. I focus particularly on the use of religious imagery and metaphor by scientists as they seek to convince the public of the power of genes or to allay concerns about new technologies. I suggest that their use of God talk may reflect both its wider prevalence in political rhetoric in the United States anti its instrumental utility in light of the religious implications of contemporary biology. [ABSTRACT FROM AUTHOR]

Gene drive is an emerging biotechnology with applications in global health, conservation and agriculture. Scientists are preparing for field trials, triggering debate about when and how to release gene-drive organisms. These decisions depend on public understandings of gene drive, which are shaped by language. While some studies on gene drive communication assume the need to persuade publics of expert definitions of gene drive, we highlight the importance of meaning-making in communication and engagement. We conducted focus groups with humanities and science teachers in the United Kingdom and United States to explore how different media framings stimulated discussions of gene drive. We found diversity in the value of these framings for public debate. Interestingly, the definition favoured by gene drive scientists was the least popular among participants. Rather than carefully curating language, we need opportunities for publics to make sense and negotiate the meanings of a technology on their own terms. [ABSTRACT FROM AUTHOR]

This paper discusses the morality of patenting human genes and genetic technologies. After examining arguments on different sides of the issue, the paper concludes that there are, at present, no compelling reasons to prohibit the extension of current patent laws to the realm of human genetics. However, since advances in genetics are likely to have profound social implications, the most prudent course of action demands a continual reexamination of genetics laws and policies in light of ongoing developments in science and technology.

The authors comment on their paper "Expression of a Multidrug Resistance Gene in Human Cancers" that was published in the 1989 issue of the "Journal of the National Cancer Institute." They said that every drug resistance mechanism has a fitness cost for the cells that are deploying such mechanisms. They added that knowledge about the expression of P-glycoprotein (P-gp) in cancers has resulted in significant changes in the drug development process.

Clostridium perfringens type F food poisoning (FP) strains produce C. perfringens enterotoxin (CPE) to cause a common bacterial food-borne illness in the United States. During FP, CPE is synthesized in the intestines when C. perfringens sporulates. Besides CPE, FP strains also produce sialidases. Most FP strains carry their cpe gene on the chromosome and all surveyed chromosomal cpe (c-cpe) FP strains produce NanH sialidase or both NanJ and NanH sialidases. NanR has been shown previously to regulate sialidase activity in non-FP strains. The current study investigated whether NanR also regulates sialidase activity or influences sporulation and CPE production for c-cpe FP strains SM101 and 01E809. In sporulation medium, the SM101 nanR null mutant showed lower sialidase activity, sporulation, and CPE production than its wild-type parent, while the 01E809 nanR null mutant showed roughly similar sialidase activity, sporulation, and CPE production as its parent. In vegetative medium, the nanR null mutants of both strains produced more spores than their parents while NanR repressed sialidase activity in SM101 but positively regulated sialidase activity in 01E809. These results demonstrate that NanR regulates important virulence functions of c-cpe strains, with this control varying depending on strain and culture conditions. [ABSTRACT FROM AUTHOR]

Cannabis use in the United States is increasing, with highest consumption among men at their peak reproductive years. We previously demonstrated widespread changes in sperm DNA methylation with cannabis exposure in humans and rats, including genes important in neurodevelopment. Here, we use an in vitro human spermatogenesis model to recapitulate chronic cannabis use and assess DNA methylation at imprinted and autism spectrum disorder (ASD) candidate genes in spermatogonial stem cell (SSC)- and spermatid-like cells. Methylation at maternally imprinted genes SGCE and GRB10 was significantly altered in SSC- and spermatid-like cells, respectively, while PEG3 was significantly differentially methylated in spermatid-like cells. Two of ten randomly selected ASD candidate genes, HCN1 and NR4A2, had significantly altered methylation with cannabis exposure in SSC-like cells. These results support our findings in human cohorts and provide a new tool with which to gain mechanistic insights into the association between paternal cannabis use and risk of ASD in offspring. [ABSTRACT FROM AUTHOR]

Recent advances in next generation sequencing along with high hopes for genomic medicine have inspired interest in genomic research with the newly dead. However, applicable law does not adequately determine ethical or policy responses to such research. In this paper we propose that such research stands at a crossroads between other more established biomedical clinical and research practices. In addressing the ethical and policy issues raised by a particular research project within our institution comparatively with these other practices, we illustrate the moral significance of paying careful heed to where one looks for guidance in responding to ethical questions raised by a novel endeavor. [ABSTRACT FROM AUTHOR]

Gene drives have already challenged governance systems. In this case study, we explore the International Genetically Engineered Machine (iGEM) competition's experiences in gene drive-related research and lessons in developing, revising, and implementing a governance system. iGEM's experiences and lessons are distilled into 6 key insights for future gene drive policy development in the United States: (1) gene drives deserve special attention because of their potential for widescale impact and remaining uncertainty about how to evaluate intergenerational and transboundary risks; (2) an adaptive risk management approach is logical for gene drives because of the rapidly changing technical environment; (3) review by individual technical experts is limited and may fail to incorporate other forms of expertise and, therefore, must be complemented with a range of alternative governance methods; (4) current laboratory biosafety and biosecurity review processes may not capture gene drive research or its components in practice even if they are covered theoretically; (5) risk management for research and development must incorporate discussions of values and broader implications of the work; and (6) a regular technology horizon scanning capacity is needed for the early identification of advances that could pose governance system challenges. [ABSTRACT FROM AUTHOR]

The article focuses on the DNA sequence variants that influence gene expression and disease risk in the U.S. It is pointed out that the effects of variations in DNA sequence are often subtle, such as altered levels of gene expression. Moreover, it is said that identifying those DNA sequences that determine levels of expression across individuals could have great medical potential. It also discusses one paper that illustrates the identification of DNA sequences which looks at the two major contractile proteins of the human heart.

Abstract: This paper contributes an empirically-based analysis of how women negotiate reproductive desires and constructions of risk in light of genetic information for a single-gene disorder with known inheritance patterns. Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and female carriers have a 50% probability with each pregnancy of transmitting the FX gene. We present data from interviews conducted with 108 mothers across the U.S. who participated in a longitudinal, mixed methods study on family adaptations to FXS and who have at least one child with FXS. Women’s accounts of their reproductive desires, actions, and reasoning indicate that the known 50% risk of transmitting the FX gene was a powerful deterrent to attempting to have more children through unmediated pregnancy. The majority (77%) decided not to have any more biological children after carrier diagnosis. This decision often required revising previous plans for how many children they would have, how and when they would have them, and what kind of mothers they would be. However, genetic risk was not a primary consideration in the reproductive calculations of 22 women who chose to continue planned and unplanned unmediated pregnancies. Though women’s reproductive negotiations are constrained by medical discourse and practices, they are also unpredictable and emerge out of lived experiences and sometimes ambivalent ways of reckoning. While increased availability and accuracy of genetic information and testing contribute to certain forms of family planning that prioritize genetic risk management, we also find that some families call upon alternative understandings and desires for making a family to articulate genetic risk and negotiate their reproductive futures. [Copyright &y& Elsevier]

Information about several papers discussed at a meeting sponsored by the Foundation for Ichthyosis and Related Skin Types Inc. (FIRST) on ichthyosis held in June 2010 in the U.S. is presented. Topics include the different methods to utilize scarce resources to advance research in ichthyosis, the identification of genes associated with human disease, and the causes for the normal-appearing skin for ichthyosis. The meeting featured several researchers including Leonard Milstone.The Foundation for Ichthyosis and Related Skin Types, Inc.™ ("FIRST") is a non-profit charitable organization.

Since 1992 the USPTO has been issuing gene patents based on the premise that a gene sequence consists of patentable subject matter and meets the requirements set forth in 35 USC § 101 et seq. Various scholars and international societies have recently questioned the USPTO's stance, raising both normative concerns as well substantive problems associated with the number and scope of gene patents on the availability and access of diagnostic tests as well as their effect on scientific innovation and method validation. This paper examines recent Congressional testimony, USPTO's deference to Congress' inaction, and the possibility of judicial remedy through currently pending litigation of Association for Molecular Pathology et. al. v. United States Patent and Trademark Office, et. al. The author argues that the pending litigation may, and should, break the current stalemate and prompt re-examination of the current US patenting guidelines to arrive at a solution that integrates important policy considerations related to innovation, access, and validation. [ABSTRACT FROM AUTHOR]

Cystathionine beta-synthase (CBS) deficiency is a rare autosomal recessive disorder that is the most frequent cause of clinical homocystinuria. Patients not treated in infancy have multi-systems disorders including dislocated lenses, mental deficiency, osteoporosis, premature arteriosclerosis, and thrombosis. In this paper, we examine the relationship of the clinical and biochemical phenotypes with the genotypes of 12 CBS deficient patients from 11 families from the state of Georgia, USA. By DNA sequencing of all of the coding exons we identified mutations in the CBS genes in 21 of the 22 possible mutant alleles. Ten different missense mutations were identified and one novel splice-site mutation was found. Five of the missense mutations were previously described (G307S, I278T, V320A, T353M, and L101P), while five were novel (A226T, N228S, A231L, D376N, Q526K). Each missense mutation was tested for function by expression in S. cerevisiae and all were found to cause decreased growth rate and to have significantly decreased levels of CBS enzyme activity. The I278T and T353M mutations accounted for 45% of the mutant alleles in this patient cohort. The T353M mutation, found exclusively in four African American patients, was associated with a B6-nonresponsive phenotype and detection by newborn screening for hypermethioninemia. The I278T mutation was found exclusively in Caucasian patients and was associated with a B6-responsive phenotype. We conclude that these two mutations occurred after ethnic socialization and that the CBS genotype is predictive of phenotype. Hum Mutat 22:434–441, 2003. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

With the advent of the Human Genome Project and widespread fears over human cloning and medical privacy, a number of states have moved to protect genetic privacy. Oregon''s unique Genetic Privacy Act of 1995, which declared that an individual had property rights to their DNA, has provoked national and international interest and controversy. This paper critically reviews the literature on genetic privacy and gene patenting from law, philosophy, science and anthropology. The debate in Oregon, from 1995 to 2001, illustrates many of the key issues in this emerging area. Both sides of the debate invoke the property metaphor, reinforcing deterministic assumptions and avoiding more fundamental questions about the integrity of the body and self-identity. The anthropological critique of the commodification of the body, and the concept of ‘embodiment’ are useful in analyzing the debate over DNA as property. [Copyright &y& Elsevier]

Copyright of American Journal of Potato Research is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Many DNA methylation-based indicators have been developed as summary measures of epigenetic aging. We examine the associations between 13 epigenetic clocks, including 4 second generation clocks, as well as the links of the clocks to social, demographic, and behavioral factors known to be related to health outcomes: sex, race/ethnicity, socioeconomic status, obesity, and lifetime smoking pack-years.Methods: The Health and Retirement Study is the data source which is a nationally representative sample of Americans over age 50. Assessment of DNA methylation was based on the EPIC chip and epigenetic clocks were developed based on existing literature.Results: The clocks vary in the strength of their relationships with age, with each other and with independent variables. Second generation clocks trained on health-related characteristics tend to relate more strongly to the sociodemographic and health behaviors known to be associated with health outcomes in this age group.Conclusions: Users of this publicly available data set should be aware that epigenetic clocks vary in their relationships to age and to variables known to be related to the process of health change with age. [ABSTRACT FROM AUTHOR]

Objectives: Using dyadic genetic information on older couples, this study queried associations of a polygenic score for well-being with one's own as well as a partner's relationship experiences. Method: Data were from the 2010 wave of the U.S. Health and Retirement Study. Analysis was through structural equation modeling. Results: Especially among women, the genetic score was associated with individuals' own relationship experiences. Genetic externalities—linkages of one's genes with a partner's experiences—were also observed. No significant gender variations emerged. Discussion: Contrary to conceptions implicit in much of existing genetics literature—which focuses on individuals' own gene–trait associations—the interpersonal environments most crucial to life course and health outcomes are shaped by the genes of all involved actors. Genetic externalities are a central component. Implications for the life course and gene–environment literatures are discussed. [ABSTRACT FROM AUTHOR]

Purpose: To present the 6-month results of the Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Peripheral Artery Disease (STOP-PAD) trial. The trial was an attempt to alter the course of chronic limb-threatening ischemia (CLTI) with a biological agent vs placebo after successful arterial revascularization at or below the knee. Materials and Methods: The multicenter, randomized, double-blinded, placebo-controlled, phase 2B STOP-PAD trial (ClinicalTrials.gov identifier NCT02544204) randomized 109 patients (mean age 71 years; 68 men) with Rutherford category 5 or 6 CLTI and evidence of persistent impaired forefoot perfusion following recent successful revascularization to 8- (n=34) or 16-mg (n=36) intramuscular injections of a non-viral DNA plasmid-based treatment vs placebo (n=34). The primary efficacy outcome was the 6-month wound healing score evaluated by an independent wound core laboratory; the primary safety endpoint was major adverse limb events (MALE), a composite of major amputation plus clinically-driven target lesion revascularization at 6 months. Results: Only one-third of the patients had complete wound healing at 6 months in the placebo (31%), 8-mg injection (33%), and 16-mg injection (33%) groups. In addition, the observed increase in the toe-brachial index from baseline to 6 months was statistically significant in each group; however, this did not result in lower rates of MALE at 6 months (24% in the placebo, 29% in the 8-mg injection, and 11% in the 16-mg injection groups). During the 6-month period, 6 patients (6%) died, and 24 patients (23%) had an amputation [only 4 (4%) major]. Conclusion: Combining revascularization and biological therapy failed to improve outcomes in CLTI at 6 months. STOP-PAD has provided insights for future trials to evaluate biological therapy. [ABSTRACT FROM AUTHOR]

Key message: A new powdery mildew resistance gene that can be readily used in wheat breeding, Pm65, was identified in the facultative wheat cultivar Xinmai 208 and mapped to the terminal region of chromosome 2AL. Wheat powdery mildew, a widely occurring disease caused by the biotrophic fungus Blumeriagraminis f. sp. tritici (Bgt), poses a serious threat to wheat production. A high breeding priority is to identify powdery mildew resistance genes that can be readily used either alone or in gene complexes involving other disease resistance genes. An F2 population and 227 F2:3 families derived from the cross Xinmai 208 × Stardust were generated to map a powdery mildew resistance gene in Xinmai 208, a high-yielding Chinese wheat cultivar. Genetic analysis indicated that Xinmai 208 carries a single dominant powdery mildew resistance gene, designated herein Pm65, and linkage analysis delimited Pm65 to a 0.5 cM interval covering 531.8 Kb (763,289,667–763,821,463 bp) on chromosome 2AL in the Chinese Spring reference sequence. An allelism test indicated that Pm65 is a new gene about 10.3 cM distal to the Pm4 locus. Pm65 was 0.3 cM proximal to Xstars355 and 0.2 cM distal to Xstars356. It conferred near-immunity to 19 of 20 Bgt isolates collected from different wheat-growing regions of the USA. Coming from a high-yield potential cultivar, Pm65 can be directly used to enhance powdery mildew resistance in wheat. The newly developed SSR markers Xstars355 and Xstars356 have the potential to tag Pm65 for wheat improvement. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the occurrence, the genetic environment and the functionality of novel variants of the MDR gene cfr(C) in Campylobacter from China.Methods: A total of 370 Campylobacter isolates of porcine and chicken origin collected from three regions of China in 2015 were screened for cfr(C) by PCR. The phenotypes and genotypes of cfr(C)-positive isolates were investigated by antimicrobial susceptibility testing, PFGE, MLST, S1-PFGE, Southern blotting and WGS. Quantitative RT-PCR was used to compare the expression levels of the cfr(C) variants in their original isolate and clone constructs in Campylobacter jejuni NCTC 11168.Results: Four (1.1%) porcine Campylobacter coli isolates were positive for cfr(C). They failed to show elevated MICs of phenicols. The deduced Cfr(C) sequences identified exhibited 2-6 amino acid changes compared with the original Cfr(C) reported in the USA. Cloning of the cfr(C) variant genes into C. jejuni NCTC 11168 resulted in ≥32-fold increases in the MICs of phenicols, indicating that the cfr(C) variant genes are functional. The cfr(C)-carrying isolates belonged to three genotypes and WGS analysis revealed the cfr(C) genes were chromosomally located in MDR genomic islands, which contained multiple antibiotic resistance genes of Gram-positive origin.Conclusions: This study identified chromosomal cfr(C) genes in C. coli isolates from China. They appeared functionally dormant in the original isolates but were fully functional when cloned and expressed in C. jejuni. The cfr(C) genes were co-transferred with other antibiotic resistance genes, possibly from Gram-positive bacteria. These findings reveal new insights into the function and transmission of cfr(C) in Campylobacter. [ABSTRACT FROM AUTHOR]

Introduction: Cigarette smoking is one of the largest causes of preventable death worldwide. This study aimed to identify susceptibility loci for age at smoking initiation (ASI) by performing an exome-wide association analysis.Methods: A total of 2510 smokers of either African-American (AA) or European-American (EA) origin were genotyped and analyzed at both the single nucleotide polymorphism (SNP) and gene levels. After removal of those SNPs with a minor allele frequency (<0.01), 48091 and 34933 SNPs for AAs and EAs, respectively, were used to conduct a SNP-based association analysis. Gene-based analyses were then performed for all SNPs examined within each gene. Further, we estimated the proportion of variance explained by all common SNPs included in the analysis.Results: The strongest signals were detected for SNPs rs17849904 in the pitrilysin metallopeptidase 1 gene (PITRM1) in the AA sample (p = 9.02 × 10-7) and rs34722354 in the discoidin domain of the receptor tyrosine kinase 2 gene (DDR2) in the EA sample (p = 9.74 × 10-7). Both SNPs remained significant after Bonferroni correction for the number of SNPs tested. Subsequently, the gene-based association analysis revealed a significantly associated gene, DHRS7, in the AA sample (p = 5.00 × 10-6), a gene previously implicated in nicotine metabolism.Conclusions: Our study revealed two susceptibility loci for age of smoking initiation in the two ethnic samples, with the first being PITRM1 for AA smokers and the second DDR2 for EA smokers. In addition, we found DHRS7 to be a plausible candidate for ASI in the AA sample from our gene-based association analysis.Implications: PITRM1 and DHRS7 for African-American smokers and DDR2 for European-American smokers are new candidate genes for smoking initiation. These genes represent new additions to smoking initiation, an important but less studied phenotype in nicotine dependence research. [ABSTRACT FROM AUTHOR]

Background Trypanosoma cruzi is a zoonotic pathogen of increasing relevance in the USA, with a growing number of autochthonous cases identified in recent years. The identification of parasite genotypes is key to understanding transmission cycles and their dynamics and consequently human infection. Natural T. cruzi infection is present in captive nonhuman primate colonies in the southern USA. Methods We investigated T. cruzi genetic diversity through a metabarcoding and next-generation sequencing approach of the mini-exon gene to characterize the parasite genotypes circulating in nonhuman primates in southern Louisiana. Results We confirmed the presence of T. cruzi in multiple tissues of 12 seropositive animals, including heart, liver, spleen and gut. The TcI discrete typing unit (DTU) predominated in these hosts, and specifically TcIa, but we also detected two cases of coinfections with TcVI and TcIV parasites, unambiguously confirming the circulation of TcVI in the USA. Multiple mini-exon haplotypes were identified in each host, ranging from 6 to 11. Conclusions The observation of multiple T. cruzi sequence haplotypes in each nonhuman primate indicates possible multiclonal infections. These data suggest the participation of these nonhuman primates in local parasite transmission cycles and highlight the value of these naturally infected animals for the study of human Chagas disease. [ABSTRACT FROM AUTHOR]

Key message: A new powdery mildew resistance gene conferring a wide spectrum of resistance toBgtisolates in the USA,Pm63, was identified in Iranian wheat landrace PI 628024 and mapped to the terminal region of the long arm of chromosome 2B. Powdery mildew is a globally important wheat disease causing severe yield losses, and host resistance is the preferred strategy for managing this disease. The objective of this study was to characterize a powdery mildew resistance gene in Iranian landrace PI 628024, which exhibited a wide spectrum of resistance to representative Blumeria graminis f. sp. tritici (Bgt) isolates collected from different regions of the USA. An F2 population and F2:3 lines derived from the cross PI 628024 × CItr 11349 were used in this study, and genetic analysis indicated that a single dominant gene, designated Pm63, conferred resistance to Bgt isolate OKS(14)-B-3-1. Linkage analysis located Pm63 to an interval of about 13.1 Mb on the long arm of chromosome 2B, spanning 710.3–723.4 Mb in the Chinese Spring reference sequence. Bin mapping assigned Pm63 to the terminal bin 2BL6-0.89-1.0, 1.1 cM proximal to STS marker Xbcd135-2 and 0.6 cM distal to SSR marker Xstars419. Allelism tests indicated that Pm63 is a new powdery mildew resistance gene, which differs from other genes in the terminal bin by origin, genomic location, and responses to a set of 16 representative US Bgt isolates. Pm63 can be widely used to enhance powdery mildew resistance in the Great Plains, western, and southeastern regions of the USA. [ABSTRACT FROM AUTHOR]

Summary: Background: Restrictive feeding is implicated in pediatric obesity, and caregivers increase controlling feeding practices on the basis of higher child weight status. However, few studies have examined how child genetic and parenting characteristics together impact restrictive feeding. Objectives: We examined whether child body mass index (BMI) status predicts caregiver use of restrictive feeding and if this association is moderated by (i) caregiver strategies to manage their children's distress and (ii) child variations in the catechol‐O‐methyltransferase (COMT) gene (Val158Met, rs4680). Methods: Participants included 126 Caucasian children (50% girls) and their caregivers who were participating in a larger study in the USA. Caregivers reported on their feeding practices and responses to child distress when children were 2.5–3.5 years of age. Child anthropometric measurements were also obtained. Restrictive feeding was assessed again 1–1.5 years later. Genomic DNA was obtained from saliva samples, and COMT‐rs4680 was genotyped using TaqMan® methodology. Results: Child BMI percentile predicted subsequent caregiver restrictive feeding for children who were Met/Met and who had caregivers reporting higher use of negative responses to child distress. For Val carriers, BMI percentile predicted restrictive feeding when caregivers were below the mean on these responses. Conclusions: Caregivers are at risk for use of restrictive feeding practices when their children are at higher BMI percentiles, and this association increases when caregivers use more ineffective stress regulation practices and their children are homozygous for the Met allele. Prevention programmes might focus on parenting behaviours that foster emotion regulation and consider variation in child responses to parenting. [ABSTRACT FROM AUTHOR]

Abstract: New techniques for the genetic modification of organisms are creating new strategies for addressing persistent public health challenges. For example, the company Oxitec has conducted field trials internationally—and has attempted to conduct field trials in the United States—of a genetically modified mosquito that can be used to control dengue, Zika, and some other mosquito‐borne diseases. In 2016, a report commissioned by the National Academies of Sciences, Engineering, and Medicine discussed the potential benefits and risks of another strategy, using gene drives. Driving a desired genotype through a population of wild animals or insects could lead to irreversible genetic modification of an entire species. The NASEM report recommends community, stakeholder, and public engagement about potential uses of the technology, and it argues that the engagement should occur as research advances, well before gene drives are deployed. Yet what “engagement” means in practice is unclear. This article seeks clarity on this problem by offering a justification for community engagement and drawing out implications of this argument for the implementation and desired outcomes of community engagement.Community engagement is essential when it comes to research that would release genetically modified insects or animals into the environment. By contrast, obtaining informed consent from people who live near such a proposed field trial is neither necessary nor sufficient. Drawing on the epistemic and moral arguments for deliberative democracy, I propose two discrete mechanisms of community engagement: community advisory boards and deliberative forums, neither of which has been systematically incorporated into research governance. The proposed mechanisms would engender respect for persons who live near field trials, even when the results of deliberation override some individuals’ preferences. Community engagement foregrounds the community in our thinking about humans’ relationship to nature, and it implies that deciding to release genetically modified insects or animals into the wild ought to be a collective decision, not one made by product developers, policy‐makers, private companies, research funders, or scientists alone. [ABSTRACT FROM AUTHOR]

Heritability is often estimated by decomposing the variance of a trait into genetic and other factors. Interpreting such variance decompositions, however, is not straightforward. In particular, there is an ongoing debate on the importance of genetic factors in cancer development, even though heritability estimates exist. Here we show that heritability estimates contain information on the distribution of absolute risk due to genetic differences. The approach relies on the assumptions underlying the conventional heritability of liability model. We also suggest a model unrelated to heritability estimates. By applying these strategies, we describe the distribution of absolute genetic risk for 15 common cancers. We highlight the considerable inequality in genetic risk of cancer using different metrics, e.g., the Gini Index and quantile ratios which are frequently used in economics. For all these cancers, the estimated inequality in genetic risk is larger than the inequality in income in the USA. [ABSTRACT FROM AUTHOR]

The Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure (InterGEN) study aims to delineate the independent and interaction effects of genomic (genetic and epigenetic) and psychological–environmental (maternally perceived racial discrimination, mental health, and parenting behavior) factors on blood pressure (BP) among African American mother–child dyads over time. The purpose of this article is to describe the two-step genetic and epigenetic approach that will be executed to explore Gene × Environment interactions on BP using a longitudinal cohort design. Procedure for the single collection of DNA at Time 1 includes the use of the Oragene 500-format saliva sample collection tube, which provides enough DNA for both the Illumina Multi-Ethnic Genotyping and 850K EPIC methylation analyses. BP readings, height, weight, percentage of body fat, and percentage of body water will be measured on all participants every 6 months for 2 years for a total of 4 time points. Genomic data analyses to be completed include multivariate modeling, assessment of population admixture and structure, and extended analyses including Bonferroni correction, false discovery rate methods, Monte Carlo approach, EIGENSTRAT methods, and so on, to determine relationships among both main and interaction effects of genetic, epigenetic, and psychological environmental factors on BP. [ABSTRACT FROM AUTHOR]